title: Terminal arbor degeneration--a novel lesion produced by the antineoplastic agent paclitaxel.
abstract: The antineoplastic agent paclitaxel causes a dose-limiting distal, symmetrical, sensory peripheral neuropathy that is often accompanied by a neuropathic pain syndrome. In a low-dose model of paclitaxel-evoked painful peripheral neuropathy in the rat, we have shown that the drug causes degeneration of intraepidermal nerve fibers (IENFs), i.e. the fibers which give rise to the sensory afferent's terminal receptor arbor. However, we did not find any evidence for axonal degeneration in samples taken at the mid-nerve level. Here we aimed to determine whether the absence of degenerating peripheral nerve axons was due to sampling a level that was too proximal. We used electron microscopy to study the distal-most branches of the nerves innervating the hind paw glabrous skin of normal and paclitaxel-treated rats. We confirmed that we sampled at a time when IENF degeneration was prominent. Because degeneration might be easier to detect with higher paclitaxel doses, we examined a four-fold cumulative dose range (8-32 mg/kg). We found no evidence of degeneration in the superficial subepidermal axon bundles (sSAB) that are located just a few microns below the epidermal basal lamina. Specifically, for all three dose groups there was no change in the number of sSAB per millimeter of epidermal border, no change in the number of axons per sSAB and no change in the diameter of sSAB axons. We conclude that paclitaxel produces a novel type of lesion that is restricted to the afferent axon's terminal arbor; we name this lesion 'terminal arbor degeneration'.
authors.affiliation: Department of Anesthesia, McGill University, Montréal, Québec, Canada. gary.bennett@mcgill.ca
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Bennett
authors.forename: Guo K
authors.initials: GK
authors.lastname: Liu
authors.forename: Wen H
authors.initials: WH
authors.lastname: Xiao
authors.forename: Hai W
authors.initials: HW
authors.lastname: Jin
authors.forename: Chiang
authors.initials: C
authors.lastname: Siau
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001522:Behavior, Animal / Q000502:physiology; D004817:Epidermis / Q000294:innervation; D008297:Male; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology; D009412:Nerve Fibers / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D009437:Neuralgia / Q000139:chemically induced / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology*; D010147:Pain Measurement; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel